Iatrogenic hypoglycemia causes recurrent physical morbidity, and some mortality and often causes psychosocial morbidity in patients with insulin dependent diabetes mellitus (IDDM). It is the result of an interplay between therapeutic insulin excess and compromised glucose counterregulation: Deficient epinephrine responses to falling glucose levels in the setting of absence of glucagon responses cause the syndrome of defective glucose counterregulation. The investigator has been at the forefront of research describing this pathophysiology and the documentation that recent antecedent hypoglycemia is a major cause of the syndrome of hypoglycemia unawareness which he described. Because these two syndromes are associated with high frequency of hypoglycemia, and tend to segregate together clinically and share several pathophysiological features including reduced autonomic (at least adrenomedullary and parasympathetic) and symptomatic responses to a given degree of hypoglycemia, these syndromes have been conceptualized by the investigator as examples of hypoglycemia-associated autonomic failure in IDDM. This is thought to be a functional disorder distinct from classical diabetic autonomic neuropathy that is largely the result of iatrogenic hypoglycemia. To pursue insight into the impact and mechanisms of the latter, four hypotheses will be tested: 1) Episodic hypoglycemia increases the frequency of subsequent iatrogenic hypoglycemia in the clinical setting in patients with IDDM. 2) Whereas glycemic thresholds for several neuroendocrine responses to and symptoms of hypoglycemia are elevated (lower plasma glucose concentrations required), glycemic thresholds for hypoglycemic cognitive dysfunction are not altered following recent antecedent hypoglycemia. 3) Glycemic thresholds for sympathetic neural responses to hypoglycemia, like those for adrenomedullary and parasympathetic neural responses, are elevated (lower plasma glucose concentrations required) following recent antecedent hypoglycemia. 4) Blood-to-brain glucose transport is reduced in patients with poorly controlled IDDM, and is increased following recent antecedent hypoglycemia in patients with IDDM. The methods used will include hyperinsulinemic, hypoglycemic clamps with quantitation of neuroendocrine (including autonomic), symptomatic and cognitive responses, measurements of sympathetic neural activity by isotope dilution (forearm norepinephrine appearance) and assessment of brain glucose transport and metabolism with (1-11C) glucose and positron emission tomography in patients with IDDM and nondiabetic controls. The data obtained may expand the body of knowledge fundamental to the development of therapeutic strategies that could improve the lives of people with IDDM by reducing the frequency of iatrogenic hypoglycemia.